July 30, 2022
Interpretation of laboratory tests in transgender and gender-diverse (TGD) people can be challenging in routine care, especially when analytes have sex-specific reference ranges. Clinicians might be challenged on whether to use reference ranges based on assigned sex, affirmed gender or a combined approach. Factors such as whether the person receives gender-affirming hormone therapy (GAHT) and for how long can affect this decision. Correct interpretation can be vital for clinical decision-making.
Endocrinologists at Mayo Clinic's Transgender and Intersex Specialty Care Clinic (TISCC) recently studied changes in kidney function in TGD people receiving GAHT. The study evaluated the effect of GAHT on serum creatinine (Cr) in TGD patients seeking care at the clinic. Findings of this study were published in Endocrine Practice in January 2022.
"As the population of gender-diverse people seeking care increases, it is imperative that we understand the limitations of applying gender-normative reference ranges in the transgender and gender-diverse population," says Arvind Maheshwari, M.B.B.S., Endocrinology, Diabetes, Metabolism, and Nutrition, at Mayo Clinic in Rochester, Minnesota. The authors found that Cr values decreased in transgender women receiving feminizing hormonal therapy, which commonly involves estradiol and anti-androgen medications such as spironolactone.
Andrea G. Kattah, M.D., Nephrology and Hypertension, at Mayo Clinic in Rochester, Minnesota, explains, "A decrease in Cr of 0.10 was noted at six months, and a more pronounced decrease was noted to occur with higher levels of serum estradiol and higher doses of estradiol. Correspondingly, Cr values increased in transgender men receiving masculinizing hormonal therapy with testosterone, with Cr values increasing 0.21 at six months. The changes noted in creatinine were likely multifactorial, including direct effects of sex steroids on the kidney and the potential hormonal effect on muscle mass due to changes in testosterone levels.
"As nephrologists, accurate measurement of kidney function helps us further predict and detect evidence of kidney dysfunction in this understudied and underserved population," says Virginia (Ginny) A. Dines, M.D., Nephrology and Hypertension, at Mayo Clinic in Rochester, Minnesota. "Patients with preexisting borderline kidney function or who have complex clinical situations such as transplant evaluation especially deserve precise assessment."
There certainly are limitations with the use of Cr and glomerular filtration rate as indicators of kidney function. The equations that include both Cr and cystatin C have the highest accuracy compared with the measured glomerular filtration rate. Therefore, the authors are pursuing additional studies with the goal to measure the effects of GAHT on cystatin C and serum creatinine in a prospective manner.
Caroline J. Davidge-Pitts, M.B., B.Ch., Endocrinology, Diabetes, Metabolism, and Nutrition, at Mayo Clinic in Rochester, Minnesota, notes: "To best help our transgender and gender-diverse patients, we need to understand expected changes in common laboratory tests with gender-affirming hormone therapy so that we do not over- or underdiagnose medical issues as these changes occur." Dr. Davidge-Pitts also states that the ideal clinical scenario would be to have transgender-specific reference ranges.
The authors concluded that Cr values established at six months after beginning GAHT could serve as baseline values going forward. Additionally, further studies are needed to understand why these changes are occurring, to determine the role of gonadectomy in kidney function and to evaluate use of markers such as cystatin C that are not related to muscle mass.
For more information
Transgender and Intersex Specialty Care Clinic. Mayo Clinic.
Maheshwari A, et al. The effect of gender-affirming hormone therapy on serum creatinine in transgender individuals. Endocrine Practice. 2022;28:52.
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